It is the aim of the proposed studies to determine the mode of inheritance of juvenile onset insulin-dependent diabetes mellitus (IDDM), to localize a diabetogenic gene locus on the sixth chromosome, to identify markers for the majority of diabetogenic genes in the general population, and to determine whether other genes are acting to effect expression of the diabetogenic genes. If evidence for such modifying genes is found, the chromosomal location and identity of such modifying genes will be explored. From these studies we hope eventually to explore the nature of the diabetogenic gene(s) and its/their interaction with environmental factors, including viruses, perhaps as a genetically determined distortion of the immune response.